In the animal studies outlined in this grant proposal, the aim is to selectively damage the perikaryia of anterior horn and spinal ganglia neurons permanently without damage to distal axons. If segmental demyelination occurs, we will study the histologic sequence of events. The results will be compared to our previous observations in human neuropathy. If segmental demyelination in peripheral nerve can be produced from chronic perikaryial damage, then the correctness of the concept of a secondary form of segmental demyelination will have been established. If it can be shown that segmental demyelination may be secondary to axis cylinder abnormality, then conceivably onion-bulb formation may be due to fluctuating alterations in the volume, morphology or other abnormality of the axis cylinder. Using experimental models in which the perikaryia of cells are repeatedly damaged, we will test this hypothesis. Several experimental neuropathy models such as lead and diphtheritic neuropathy are considered to have segmental demyelination as the predominant histologic type of myelinated fiber change. However, both lead and diphtheritic neuropathy in man are know to have as the commonest change linear rows of myelin ovoids not discontinuous loss of myelin with preserved axis cylinders. We would like to produce these disorders in experimental animals to see whether the segmental demyelination, which undoubtedly occurs, can be accounted for by changes in axis cylinders. Cadmium neuropathy will be studied since it is thought to produce a limited lesion in spinal ganglia. Peripheral nerves will be studied for the histologic sequence of events in fiber degeneration for the presence of secondary segmental demyelination.